Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States

Background & Aims: In the absence of other causes, overweight and obesity increase the risk of liver disease. We examined whether central adiposity and metabolic markers explain the association of body mass index (BMI as kg/m(2)) with abnormal serum alanine aminotransferase (ALT) activity in a national, population-based study. Methods: Adult participants (5724) in the third U.S. National Health and Nutrition Examination Survey (1988-1994) underwent anthropometric measures and phlebotomy after an overnight fast. Participants with excessive alcohol consumption, hepatitis B, hepatitis C, iron overload, or known diabetes were excluded. Results: Elevated ALT levels were found in 2.8% of the population. In univariate analysis, factors associated with elevated ALT levels (P < 0.05) included younger age, male sex, Mexican-American ethnicity, and higher BMI, waist-to-hip circumference ratio (WHR), and fasting serum leptin, triglyceride, insulin, and glucose concentrations. The proportion of elevated ALT activity due to overweight and obesity (BMI greater than or equal to25 kg/m(2)) was 65%. In multivariate logistic regression analysis, control for WHR, demographic factors, and glucose concentration diminished but did not eliminate the association of higher BMI with elevated ALT activity. After adding leptin and insulin concentrations, abnormal ALT activity was most strongly associated with higher WHR (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.12-:1.56) and leptin (OR, 1.12; 95% CI, 1.01-1.24) and insulin (OR, 1.27; 95% CI, 1.01-1.60) concentrations, whereas BMI was not independently related. Conclusions: In this large, national, population-based study, central adiposity, hyperleptinemia, and hyperinsulinemia were the major determinants of the association of overweight with elevated serum ALT activity.